Influenza and pneumonia are the most common infection-related and vaccine-preventable causes of hospitalization and death. Over 90% of influenza-related deaths occur among the 13% of adults aged >65 years. Over 2 million Americans reside in nursing homes, skilled nursing facilities, or long-term residential care facilities, a number the CDC projects will significantly grow in the coming decades. These seniors rank highest for risk of influenza complications. Two influenza vaccines now available are FDA approved specifically for persons over age 65: the newly approved adjuvanted seasonal influenza vaccine (Fluad) and the increasingly used high dose (HD(FluzoneHD)) vaccine approved in 2009. The absolute or relative clinical advantage to long-term care residents of Fluad vs. HD over non-adjuvanted standard dose (SD) vaccine remains unclear from existing immunologic and clinical evidence. Fluad and HD have not been compared head-to-head and an industry-sponsored study is unlikely to be conducted to evaluate relative efficacy or effectiveness due to uncertainty as to whether manufacturers will gain additional market advantage while risking uncovering relative inferiority. Both Fluad and HD vaccine have been shown individually to be more effective than SD vaccine in trials conducted in different cohorts and years. HD vaccine is more expensive than SD vaccine, and Fluad is less expensive than HD vaccine. As an adjuvanted vaccine, Fluad has been shown to have higher levels of heterologous immunity to drifted influenza strains than non-adjuvanted (SD) vaccine - another potential advantage of Fluad over HD vaccine, which is non-adjuvanted. Heterologous immunity is particularly important in bad match years when the CDC's strain choices for vaccine composition in that season are incorrect. Also, adjuvant is used in vaccines in general to maintain higher antibody titers for a longer period of time. This project's rationale and innovation derive from its ability to help determine the best use of these two vaccines in the setting of one of the most vulnerable elderly populations - those living in long-term care (LTC) settings such as nursing homes (NH). Overall the immunogenicity and clinical analyses they propose here are essential to provide support and rationale as to whether an enormously more expensive multi-site clinical endpoint RCT to compare these two vaccines is warranted. Hypothesis: Adjuvanted flu vaccine, Fluad, is not immunologically inferior to HD influenza vaccine in older persons living in long-term care. They propose a non-inferiority randomized clinical trial to enroll 558 NH residents age 65 and older to receive either Fluad or HD vaccine at 1:1 ratio. Blood will be sampled pre- and post-vaccine (1 mo after vaccination) and after the influenza season is over for blinded laboratory analysis. Aim 1. Primary objective: To determine if Fluad is immunologically non-inferior to HD influenza vaccine in NH residents over age 65. Aim 2: Secondary objective: To determine if Fluad has greater heterologous immunity than HD vaccine. Aim 3: Pilot clinical objective: To determine if Fluad has similar protective efficacy to HD vaccine.